It is known that auditory stimulation of a subject can be used to evoke brainstem response potentials but other stimuli than auditory may be used. Auditory brainstem response audiometry is a known screening test to monitor for hearing loss or deafness.
For instance international patent application WO 2008/006164 discloses a method for acquiring an auditory brainstem response, by presenting a plurality of stimuli, detecting electrophysiological signals in response to the stimuli, a recover signal is generated based on the stimuli and the response is determined from the electrophysiological signals and the recovery signal.
Recently new applications have evolved to diagnose certain brainstem disorders.
For instance, in international patent application WO 2006/062480, of the same applicant as the present application, which hereby is incorporated in its entirety for all purposes, a system and method is disclosed for diagnosis of brainstem disorders, such as schizophrenia.
WO2007/050780 discloses monitoring systems and methods for sensing biological and other responses reflecting various aspects of the nervous system associated with specific neurologic states. Stimulatory effects on a neurologic system are assessed. One method includes stimulating the neurologic system, monitoring at least one neurologic state for effects of the stimulation to the neurologic system, gathering multi-dimensional data from the monitoring of the at least one neurological state, and analyzing the multi-dimensional data to determine multi-dimensional interactions between the stimulation and the effects on the at least one neurological state. Neurologic states assessed comprise hypnotic, analgesia, relaxation, stress, depression, anxiety, allostasis, immune response, and combinations thereof.
Neurological states may be affected by certain stimuli, including pharmaceutical stimuli. A method is disclosed in international patent application WO 2007/084979 for evaluating an effect of a psychotropic compound or a treatment on a neuronal activity of an animal including determining a change in the amount of information generated by neurons in response to at least one repeatedly applied stimulus. The change is caused by administering the psychotropic compound or a treatment. Also provided is a method of screening psychotropic compounds for effectiveness on an animal which involves using a change in sensory discrimination in a population of neurons of the animal, wherein the sensory discrimination is obtained in response to one or more stimuli repeatedly applied to the animal and wherein a change in the sensory discrimination occurs due to administering the psychotropic compounds to the animal.
U.S. Pat. No. 6,556,861 discloses A Fetal Brain Monitor (FBM) that utilizes a transducer which is placed on the abdomen of a mother and which is pulsed to generate auditory sounds, i.e., clicks, to provide auditory brainstem evoked responses (BAER) of a fetus within the mother's uterus. The fetus' brain waves are detected by a biosensor, amplified, converted to digital data, and analyzed, in one embodiment, using a digital comb filter to improve the signal/noise ratio. The computer system uses QEEG (Quantitative EEG) to compare the data from the fetus to normative data or to prior states of the fetus' own data (self-norm).
The basic idea disclosed in U.S. Pat. No. 6,556,861 is to compare the data to normative data from a population of fetuses to determine if the Brainstem Auditory Evoked Potentials are normal or abnormal. This is conducted by using unmodified clicks or pulses similar to those used for Brainstem Auditory Evoked Response monitoring. A briefly described alternative or complement to this could be to use a self-norm. The described self-norm refers to an initial recording being an initial state or a prior state of the fetus being monitored. Each successive recording being a session comprising an averaged multitude of stimuli is compared to a initial state (such as an identified start point) or prior state for determining a degree of change from the initial state. I.e. the fetal brain is assessed relative to an earlier state in the fetus to allow for a comparison of a successive measurement relative to some prior state. This is done to follow the development of the central nervous system of a fetus. The taught self-norm does not disclose repeatingly presenting to a subject a train of unmodified click within a short time span from and related to a train of modified clicks to solve the problem of having the measured data presented in absolute figures. Absolute figures is an issue and a non-desired entity when comparing for example the brainstem profile of one subject being under influence of a drug to another subject or to determine to which degree a subject responds to a certain substance. This is in particular of interest for determining the efficiency of a treatment, such as by medication taken for treating brain related diseases, like ADHD, depression, stress etc.
Moreover, the above referred prior art documents are very general. Variations between tested individuals are generally very high. The prior art disclosures do not take this into consideration. Variation is for instance caused by individually different cognitive abilities or awareness or medication effectiveness. This means that all tested subjects hitherto needed to be manually divided into groups of compatible individuals to avoid too large variations of test results. Moreover, the measurements recorded by the prior art rely on absolute values and not the effect of the tested individual. Furthermore, the stimuli applied are hard to clone or reproduce causing further variations in the recorded data. This makes it hard to perform reliable comparisons between measurements from one individual to another and by concentrating the measurements to small parts of the brain, complex patterns are missed out which could be used to see subtle variations, for example connected to pharmacology. Another drawback with the above described systems and methods are that the practitioner needs to know where to look for a certain anticipated effect since they do not cover responses from the whole brainstem.
Hence, an Improved technique for determination of brainstem response state development would be advantageous and In particular allowing for increased flexibility, cost-effectiveness, robustness, reliability and/or patient friendliness would be advantageous.